The use of hydrophilic polymers to produce sustained or modified release pharmaceutical compositions is known in the art. For modified release solid dosage forms comprising a drug dispersed uniformly in hydrophilic polymers, release of the drug is controlled primarily by diffusion of the drug, or by surface erosion of the hydrophilic polymers into the surrounding medium, or by a combination of the two processes. Control of the rate of release benefits therapy by producing constant blood levels of the active ingredient and by decreasing the frequency of administration, thereby improving patient compliance to the dosage regimen. The present invention provides a pharmaceutical composition of modified release tablets of cefaclor or cephalexin suitable for twice-daily administration to human subjects.
Several controlled drug delivery system adapted for the delivery of cefaclor or cephalexin are known in the prior art.
U.S. Pat. No. 4,968,508 discloses a sustained release matrix tablet comprising from about 0.1% by weight to 90% by weight of cefaclor, from about 5% by weight to 29% by weight of a hydrophilic polymer, and from about 0.5% by weight to about 25% by weight of an acrylic polymer which dissolves in the pH range from about 5.0 to 7.4, with the proviso that the total weight of the polymers is less than 30% by weight of the formulation. Although a specific cefaclor formulation is described, the description in the patent suggests that the formulation is suitable for any drug and is particularly suitable for cephalexin and cefaclor.
U.S. Pat. No. 4,919,938 discloses a sustained release pharmaceutical composition in tablet form consisting essentially of a core matrix containing 20% to 60% by weight of a hydroxypropylmethylcellulose gelling agent, 0.41% to 20% by weight of (+)-trans-1a,2,3,4a,5,6-hexahydro-9-hydroxy-4-(1-propyl)-4H-naphth 1,2-b!-1,4-oxazine hydrochloride, 2.08 to 12.5% by weight of buffering agent and suitable pharmaceutically acceptable excipients. A coating of a slowly soluble water permeable ethylcellulose polymer surrounds the core matrix.
U.S. Pat. No. 4,983,398 discloses a therapeutically active composition comprising a mixture of a therapeutically active medicament and a carrier base material, wherein the carrier base material consists essentially of one or more water-soluble, non-ionic cellulose ethers, wherein at least one of the cellulose ethers is a hydroxypropyl methylcellulose having a number average molecular weight of at least 50,000, and an alkali metal carboxylate. The carrier base comprises less than 30% by weight of the total weight of the composition.
U.S. Pat. No. 4,369,172 discloses a carrier base material combined with a therapeutically active medicament shaped and compressed to a solid unit dosage form having a regular and prolonged release pattern upon administration. The carrier base material is hydroxypropyl methylcellulose, or a mixture of hydroxypropyl methylcellulose and up to 30% by weight of a mixture of ethylcellulose and/or up to 30% by weight of the mixture of sodium carboxymethylcellulose, and wherein the hydroxypropyl methylcellulose has a hydroxypropyl content of 9-12% weight and a number average molecular weight of less than 50,000.
U.S. Pat. No. 4,713,247 discloses a long-acting formulation of cefaclor which comprises a mixture of a non-enteric coated component of cefaclor as a rapid-release component and an enteric coated component of cefaclor as a slow-release component at a ratio of 4:6 based upon cefaclor potency. The rapid release component contains at least one additive selected from the group consisting of lactose, sucrose, D-mannitol, corn starch, wheat starch and low-substituted hydroxypropylcellulose in an amount of up to 75 weight % based on the whole rapid release component. The slow release component contains at least one additive selected from the group consisting of lactose, sucrose, D-mannitol, corn starch, wheat starch and low-substituted hydroxypropylcellulose in an amount of up to 75 weight % based on the whole slow release component and is coated with an enteric coating film soluble in the pH range of 5.0 to 7.0.
U.S. Pat. No. 4,250,166 discloses a long-acting cephalexin preparation which comprises normal (i.e., plain, quick r?,leasing) cephalexin which dissolves rapidly in the stomach, and coated particulate cephalexin which does not dissolve in the stomach but-dissolves rapidly in the upper intestine. The coated portion is coated with a copolymer of methylmethacrylate and methacrylic acid which dissolves at a pH of from 5.5 to 6.5. The potency ratio of the normal cephalexin to the coated portion is between 40:60 and 25:75.
U.S. Pat. No.4,557,925 discloses a controlled release pharmaceutical tablet comprising a drug and a coating applied thereon. The coating comprises a film-forming forming polymer which is insoluble in water and gastrointestinal fluids and consists essentially of a terpolymer of polyvinylchloride, polyvinyl acetate and polyvinyl alcohol, and a water soluble pore creating material randomly distributed in the terpolymer coating. The pore creating substance is present in an amount of one part to 35 parts for each one to ten parts of terpolymer.
U.S. Pat. No. 4,726,951 discloses a pharmaceutical composition for oral administration with selectively adjustable programmed release and controlled absorption, comprising miniaturized granules obtained by high to very high compression. The pharmaceutical composition comprises miniaturized granules (a) containing pH control agents, (b) coated with excipients determining the slow penetration of digestive liquids, and/or (c) coated with a very thin layer of liquids or mixture of such granules, with the relative proportion of (a), (b) and (c) adjusted to give the desired release of the active ingredient. Cephalexin is one of the active ingredients disclosed.
U.S. Pat. No. 5,051,262 discloses a delayed action programmed release pharmaceutical preparation of one or more medicament units suitable for oral administration, each unit comprising an inert core surrounded by at least one inner layer and one or more inert outer coatings. At least one of the inner layers comprises an active medicament, which has a solubility which varies with pH and is either basic or acidic, and at least one pH adjuster. The pH adjuster is an organic acid or organic acid salt if the medicament is basic, or an inorganic base or basic salt if the medicament is acidic. The pH adjuster is present in an amount sufficient to ensure that the rate of dissolution of the medicament is substantially independent of the pH of the environment in which dissolution occurs. Cephalexin is described as one of the possible medicaments.